A First-in-Human Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of a Novel CRISPR RNA-editing Therapy in Patients with Mecp2 Duplication Syndrome, a Rare Orphan Disease (HERO)

Inclusion Criteria:

• Males ≥ 2 and ≤18 years at the time of signing informed consent;

• Genetic test and clinical confirmed diagnosis of MDS;

• Stable pattern of seizures, or has had no seizures while currently receiving medicaltreatment (including antiepileptics) and physical therapy are stable for at least 2months before screening;

• Willing to adhere to protocol, including biological samples collection andhospitalization for intracerebroventricular injection surgery;

• Acceptable hematology, clinical chemistry, and urine laboratory parameters.

Exclusion Criteria:

• MECP2 gene triplication;

• Concurrent genetic syndromes other than MDS;

• Significant brain or cerebellar atrophy, or other significant degenerative changesas shown in cranial MRI at screening;

• Prior or current hypertension, cardiomyopathy, myocardial ischemia or atrialfibrillation and other cardiovascular diseases;

• Prior central nervous system surgery within 6 months before enrolment;

• Systemic use of immunosuppressive drugs within 3 months before enrolment;

• Prior gene therapy or oligonucleotide therapy treatments;

• Any other conditions that would not allow the potential subject to completefollow-up examinations during the study and would, in the opinion of theinvestigator, make the potential subject unsuitable for the study.